Infection by enveloped viruses is initiated by binding of the viral envelope glycoprotein(s) to specific receptor molecules on the target cells, followed by fusion between the viral and cellular membranes. We have initiated mechanistic studies of fusion mediated by glycoproteins of paramyxoviruses: SV5, measles virus (MV), and canine distemper virus (CDV). In all cases cell fusion requires co-expression of the virus fusion (F) and hemagglutinin (HA or HN) glycoproteins on the surface of one cell, as well as the presence of the appropriate receptors on the other cell. For the morbillaviruses MV and CDV, fusion occurs efficiently with heterologous expression of F from one virus and H from the other; cell-type specificity is determined by H. We also obtained direct evidence for functional and structural interaction between measles H and CD46, the known MV receptor.